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The Journal of Membrane Biology

, Volume 1, Issue 1, pp 294–345 | Cite as

The effects of the macrotetralide actin antibiotics on the equilibrium extraction of alkali metal salts into organic solvents

  • G. Eisenman
  • S. Ciani
  • G. Szabo
Article

Summary

In order to clarify the mechanism by which neutral molecules such as the macrotetralide actin antibiotics make phospholipid bilayer membranes selectively permeable to cations, we have studied, both theoretically and experimentally, the extraction by these antibiotics of cations from aqueous solutions into organic solvents. The experiments involve merely shaking an organic solvent phase containing the antibiotic with aqueous solutions containing various cationic salts of a lipid-soluble colored anion. The intensity of color of the organic phase is then measured spectrophotometrically to indicate how much salt has been extracted. From such measurements of the equilibrium extraction of picrate and dinitrophenolate salts of Li, Na, K, Rb, Cs, and NH4 into n-hexane, dichloromethane, and hexane-dichloromethane mixtures, we have verified that the chemical reactions are as simple as previously postulated, at least for nonactin, monactin, dinactin, and trinactin. The equilibrium constant for the extraction of each cation by a given macrotetralide actin antibiotic was also found to be measurable with sufficient precision for meaningful differences among the members of this series of antibiotics to be detected. It is noteworthy that the ratios of selectivities among the various cations were discovered to be characteristic of a given antibiotic and to be completely independent of the solvent used. This finding and others reported here indicate that the size and shape of the complex formed between the macrotetralide and a given cation is the same, regardless of the species of cation bound. For such “isosteric” complexes, notable simplifications of the theory become possible which enable us to predict not only the electrical properties of a membrane made of the same solvent and having the thinness of the phospholipid bilayer but also, and more importantly, the electrical properties of the phospholipid bilayer membrane itself. These predictions will be compared with experimental data for phospholipid bilayer membranes in the accompanying paper.

Keywords

Electrical Property Meaningful Difference Neutral Molecule Picrate Notable Simplification 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ciani, S., G. Eisenman, and G. Szabo. 1969. A theory for the effects of neutral carriers such as the macrotetralide actin antibiotics on the electric properties of bilayer membranes.J. Membrane Biol. 1: 1.Google Scholar
  2. Conway, B. E. 1952. Electrochemical Data. Elsevier, Amsterdam.Google Scholar
  3. Eisenman, G. 1962. Cation selective glass electrodes and their mode of operation.Biophys. J. 2: pt. 2, 259.PubMedGoogle Scholar
  4. 1965. The electrochemistry of cation selective glass electrodes. In: Advances in Analytical Chemistry and Instrumentation, vol. 4. C. N. Reilley, editor. p. 213. Wiley-Interscience, New York.Google Scholar
  5. , S. M. Ciani, and G. Szabo. 1968. Some theoretically expected and experimentally observed properties of lipid bilayer membranes containing neutral molecular carriers of ions.Fed. Proc. 27: 1289.PubMedGoogle Scholar
  6. . 1969. Theory of membrane electrode potentials: An examination of the parameters determining the selectivity of solid and liquid ion exchangers and of neutral ionsequestering molecules. Chapter 1 in:Ion-Selective Electrodes. R. A. Durst, editor. Natl. Bureau of Standards Special Publ. 314. U.S. Govt. Printing Office, Washington.Google Scholar
  7. Harned, H. S., and B. B. Owen. 1958. The Physical Chemistry of Electrolytic Solutions. Reinhold Publ. Corp., New York.Google Scholar
  8. Kilbourn, B. T., J. D. Dunitz, L. A. R. Pioda, and W. Simon. 1967. Structure of theK + complex with nonactin, a macrotetralide antibiotic possessing specificK + transport properties.J. Mol. Biol. 30: 559.PubMedGoogle Scholar
  9. Matsen, F. A. 1956. Chemical Applications of Spectroscopy. Vol. 9. of Technique of Organic Chemistry. Interscience Publ., Inc., New York.Google Scholar
  10. Pedersen, C. J. 1968. Ionic complexes of macrocyclic polyethers.Fed. Proc. 27: 1305.PubMedGoogle Scholar
  11. Pioda, L. A. R., H. A. Wachter, R. E. Dohner, and W. Simon. 1967. Komplexe von Nonactin und Monactin mit Natrium-, Kalium-und Ammonium-Ionen.Helv. Chim. Acta 50: 1373.Google Scholar
  12. Pressman, B. C., E. J. Harris, W. S. Jagger, and J. H. Johnson. 1967. Antibiotic-mediated transport of alkali ions across lipid barriers.Proc. Nat. Acad. Sci. 58: 1949.PubMedGoogle Scholar
  13. Robinson, R. A., and R. H. Stokes. 1959. Electrolyte Solutions. Butterworth, Inc. London.Google Scholar
  14. Szabo, G., G. Eisenman, and S. Ciani. 1969a. The effects of the macrotetralide actin antibiotics on the electrical properties of phospholipid bilayer membranes.J. Membrane Biol. 1: 346.Google Scholar
  15. ———. 1969b. Ion distribution equilibria in bulk phases and the ion transport properties of bilayer membranes produced by neutral macrocyclic antibiotics. In:Proc. Coral Gables Conference on the Physical Principles of Biol. Membranes, Dec. 18–20, 1968. Gordon and Breach, Science Publ., New York (in press).Google Scholar
  16. Weissberger, A., E. S. Proskauer, J. A. Riddick, and E. E. Toops, Jr. 1955. Organic solvents.In: Technique of Organic Chemistry, vol. VII. A. Weissberger, editor. Interscience Publ., Inc., New York.Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1969

Authors and Affiliations

  • G. Eisenman
    • 1
  • S. Ciani
    • 1
  • G. Szabo
    • 1
  1. 1.Department of PhysiologyUniversity of California, Medical CenterLos Angeles

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